A multicenter team of researchers, supported in part by the National Institutes of Health (NIH), has determined the complete genetic sequence of a chromosome of the most deadly malaria parasite, Plasmodium falciparum. This advance may help identify new targets for anti-malaria drugs and vaccines, which are badly needed to fight a disease that claims up to 3 million lives each year.

The new data are reported in the Nov. 6, 1998 issue of the journal Science by Malcolm J. Gardner, Ph.D., of The Institute for Genomic Research (TIGR, Rockville, Md.), Navy Captain Stephen L. Hoffman, M.D., of the Naval Medical Research Center (NMRC, Bethesda, Md.), and their colleagues at NMRC, TIGR, New York University, Johns Hopkins University, and the National Center for Biotechnology Information of the National Library of Medicine at NIH.

Drs. Gardner, Hoffman and their collaborators sequenced chromosome 2 of P. falciparum. Theirs is the first report to describe the complete genetic sequence of a parasite chromosome.

Project funding was initiated by the National Institute of Allergy and Infectious Diseases (NIAID) of NIH and the NIH Office of Research on Minority Health, and was subsequently augmented by the U.S. Department of Defense. An international consortium of agencies, including NIAID, is supporting efforts to sequence the other 13 chromosomes of this parasite.

"This sequence information promises to provide new leads to fighting malaria, a disease that exacts a huge burden worldwide, in human and economic terms," says Anthony S. Fauci, M.D., NIAID director. "This sequencing effort is part of a broad-based NIH strategy to control malaria and other important diseases that threaten global health, including tuberculosis and AIDS."

"This study demonstrates the feasibility of sequencing the entire genome of Plasmodium falciparum," adds Michael Gottlieb, Ph.D., Parasite Biology Program Officer at NIAID. "The researchers have identified more than 200 genes, many of which are probably essential to parasite functions, including genes that mediate interactions with host cells and contribute to disease.

"Of particular note, the researchers found a group of genes that encode a large family of surface proteins called rifins, which may help the parasite escape the immune response. A better understanding of these genes and their protein products will help us develop new strategies to control malaria," Dr. Gottlieb adds.

Genetic sequencing reveals the lineup of paired chemical bases that make up the pathogen's DNA - the language of life. Sequence information can be exploited in many ways, such as finding new targets for drugs, identifying the mutations that contribute to a pathogen's virulence or ability to resist drugs, and determining components of a pathogen to incorporate into vaccines.

Besides sequencing the genome of P. falciparum, NIAID-supported scientists are also obtaining DNA sequence information from the genomes of P. vivax (another of the four different plasmodium parasites that cause human malaria), and from P. berghei, which causes malaria in rodents and provides a laboratory model of human disease. NIAID also supports the sequencing of more than 20 other medically important pathogens.

Between 300 and 500 million new cases of malaria occur each year, primarily in sub-Saharan Africa. Every 30 seconds, a child dies of the disease. No effective vaccine exists to prevent malaria, and the disease has become increasingly difficult to treat because of the spread of drug resistance.

Under the leadership of NIH Director Harold Varmus, M.D., NIH has fortified its commitment to malaria research, with expanded efforts to study the genomes of malaria parasites, delineate mechanisms of drug resistance and develop a malaria vaccine.

Other important NIH malaria initiatives include:

Laboratory, field-based and clinical research in malaria pathogenesis, parasite biology, vector biology, diagnostics, immunology, and drug discovery and development. This research is conducted on the NIH campus and elsewhere in the United States, Mali, Cameroon, Ghana, Malawi, Thailand, Papua New Guinea, Indonesia and Brazil.

Participation in the Multilateral Initiative on Malaria, a global consortium that enhances international collaboration among malaria scientists around the world and identifies resources to enhance malaria research.

A repository of malaria reagents to improve access to research material for investigators worldwide.

A new communications network on the World Wide Web for the malaria research community. The URL is http://www.malaria.org.

NIAID is a component of the NIH. NIAID conducts and supports research to prevent, diagnose and treat illnesses such as HIV disease and other sexually transmitted diseases, tuberculosis, malaria, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services.

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.